Targeting Src signaling in metastatic bone disease.
Src is a tyrosine kinase involved in the regulation of a range of cellular processes including proliferation, adhesion, motility and survival. In addition, it is a key regulator of bone metabolism. Src has been implicated in the pathogenesis of a number of cancers, and has been found to be overexpressed in breast, prostate, colorectal, pancreatic and nonsmall-cell lung tumors. There is also evidence that aberrant Src signaling may contribute to the increased osteoclastic activity associated with bone metastases. Bone metastases frequently occur in cancer patients with advanced disease. The metastasized cells disrupt normal bone remodeling pathways resulting in the release of growth factors that further promote tumor growth. Thus, a cycle of metastatic bone destruction is initiated, leading to compromised skeletal integrity and substantially reduced quality of life. Because of the role of Src in both cancer development and in bone metabolism, it may provide a therapeutic target for patients with bone metastases.
Araujo
John
J
MD Anderson Cancer Center, Houston, TX 77030-3721, USA. johna@mdanderson.org
Logothetis
Christopher
C
D000818:Animals; D001859:Bone Neoplasms / Q000201:enzymology* / Q000473:pathology; D001842:Bone and Bones / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D018450:Disease Progression; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000473:pathology; D009389:Neovascularization, Pathologic; D010010:Osteoclasts / Q000378:metabolism; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism*
D019061:src-Family Kinases